"Strike the Blood II" continues the story of Kojou Akatsuki, a high school student who becomes the Fourth Primogenitor, a powerful vampire known as the "World's Mightiest Vampire." The series is set on Itogami Island, a man-made island that serves as a sanctuary for demons and humans. Kojou's life takes a dramatic turn when he encounters Yukina Himeragi, a Sword Shaman sent to monitor him due to the potential threat his powers pose. Despite initial tensions, the two form a close bond as they face various supernatural threats together.

The narrative in "Strike the Blood II" revolves around Kojou and Yukina as they confront new adversaries and uncover deeper mysteries surrounding Kojou's powers. The series introduces additional characters, including Avrora Florestina, a girl who shares a mysterious connection with Kojou's abilities, and Natsuki Minamiya, a powerful mage and Kojou's homeroom teacher. These characters play pivotal roles in the unfolding events, often aiding Kojou and Yukina in their battles.

The plot delves into the political and supernatural conflicts involving the Beast Vassals, powerful familiars tied to the Primogenitors. Kojou's growing mastery over his abilities becomes crucial as he faces off against rival factions, rogue demons, and ancient entities seeking to exploit his power. The series also explores the dynamics between Kojou and the women in his life, particularly Yukina, whose loyalty and combat skills make her an indispensable ally.

Throughout the series, themes of trust, responsibility, and the coexistence of humans and demons are explored. Kojou's journey is marked by his struggle to balance his newfound powers with his desire to protect those he cares about. The narrative maintains a balance between action-packed sequences and moments of character development, ensuring a cohesive and engaging storyline. "Strike the Blood II" builds on the foundation of its predecessor, expanding the lore and deepening the relationships between its central characters.